Topic Editor: Grant E. Fraser, M.D., FRACGP, FACRRM, ASTEM
Review Date: 2/7/2013
Definition
Methanol or "wood alcohol" when ingested in sufficient quantities has toxic effects due to formation of formic acid as part of the metabolism of methanol. The effects of formic acid include metabolic acidosis, visual impairment, neurologic sequelae, and sometimes death. The source of methanol in poisonings usually is from methanol-contaminated illicit liquor, suicidal ingestion of methanol containing products, consumption by chronic alcoholics as a substitute for ethanol, or unintended consumption by children.
Description
- Methanol is a clear, colorless solvent which is a common component of several industrial and household liquids
- It is a volatile liquid, with absorption over 30–90 minutes, with a quite prolonged half-life of approximately 8 hours
- Methanol toxicity develops in 3 phases
- Initially, inebriation due to ingestion of methanol
- Methanol is metabolized to formaldehyde by the hepatic enzyme alcohol dehydrogenase, with conversion of formaldehyde to formic acid occurring rapidly by the enzyme aldehyde dehydrogenase
- The toxic metabolite of methanol metabolism, formic acid, inhibits cytochrome oxidase in the mitochondria resulting in histotoxic hypoxia. Sensitive organs, such as the brain and visual pathways are most affected
- Formic acid accumulation results in metabolic acidosis, optic nerve demyelination, and neurological dysfunction. Toxic manifestations are usually seen 12-24 hours following methanol ingestion
Epidemiology
- Incidence/prevalence
- Methanol poisoning is relatively uncommon in the U.S., with about 1,000–2,000 cases/year are reported which accounts for <1% of all poisoning cases
- In 2010, 575 methanol exposure cases were reported with 12 deaths and 55 cases of moderate-to-severe outcomes
- Age
- Most common among individuals >18 years of age, followed by children aged <6 years
- One review in Iran found 51% of cases were aged 20-29 years old
- Gender
- Males are more commonly affected than females
- Risk factors for getting condition
- Alcoholics: Individuals may ingest methanol as a substitute for ethanol or accidentally as a component of illicit liquor
- Children: Storing methanol within reach of children poses the risk of ingestion
- Industrial workers: Accidental inhalation of methanol fumes
- Use of methanol in institutionalized settings (eg, prisons where ethyl alcohol is not readily available)
Etiology
- Ingestion or inhalation of methanol may be accidental or deliberate
- Methanol is commonly found in
- Adhesives
- Antifreeze solutions
- Carburetor cleaners
- Copy machine fluid
- Formalin
- Gasoline
- Household cleaners
- Improperly distilled liquor (moonshine)
- Industrial solvents
- Paints and varnishes
- Sterno cans
- Windshield washer fluid
- Wood alcohol
History
- Initial symptoms usually involve the central nervous system (CNS), eyes, and gastrointestinal (GI) tract
- Presenting symptoms include mild transient drowsiness and intoxication
- Headache, vertigo, lethargy, confusion, and dyspnea are also common
- GI symptoms include nausea, vomiting, and abdominal pain
- Visual disturbances, include decreased visual acuity, photophobia, blurred vision, and snowfield vision may be commonly reported
- Severely intoxicated patients may have fixed dilated pupils
- Weakness and respiratory difficulty may occur after a latent period of 12–24 hours
Physical findings on examination
Physical findings in cases of methanol poisoning may include:
- Coma
- Distinctive formalin odor detectable in the breath or urine
- Gastritis (tender epigastrium)
- Heart rate abnormalities including bradycardia in later stages
- Hypotension (often a terminal event)
- Inebriation
- Ophthalmologic findings include:
- Impaired pupillary reaction
- Loss of disc cupping on funduscopy
- Retinal edema or hyperemia
- Visual acuity impaired (blurry or double vision in some)
- Parkinson-type extrapyramidal symptoms such as bradykinesia, tremor, rigidity and mild dementia may be seen in patients with severe acute or low-level chronic methanol poisoning
- Seizures
- Stupor
- Tachypnea (to compensate for metabolic acidosis)
Blood Tests findings
Laboratory blood tests may identify the level of methanol poisoning.
- ABG or VBG for evaluation of degree of acidosis
- CBC and comprehensive panel are reasonable to review for any hematologic, electrolyte, hepatic or renal abnormalities. Elevated blood glucose >140 mg/dL (7.8 mmol/L) is more common among non-survivors of methanol poisoning
- Serum methanol and formate levels
- Serum methanol concentration measured using gas chromatography confirms the diagnosis of methanol poisoning. Such testing is generally not widely available on an emergent basis, and also require significant time for such testing even when available
- Serum formate is a more sensitive indicator of methanol poisoning after the latency period
- Serum osmolality
- Methanol increases the serum osmolar gap. For each milligram of methanol per deciliter, the osmolar gap rises by about 0.34 mOsm/kg
- Osmolar gap = measured plasma osmolality - calculated osmolality
- Calculated osmolality (mOsm/kg) = 2(Na+) + (glucose/18) + (blood urea nitrogen [BUN]/2.8
- Anion gap
- Anion gap is the difference between the sum of the measured cations and the sum of the measured anions
- As methanol metabolism proceeds, the osmolal gap decreases and the anion gap increases due to formation of formate leading to metabolic acidosis
- Anion gap metabolic acidosis is indicated by decreased serum bicarbonate level along with high lactate and ketone levels
- Serum amylase or Lipase
- Elevated level may indicate pancreatitis, which can commonly complicate methanol poisoning
Radiographic findings
- Computed tomography (CT) or magnetic resonance imaging (MRI)
- CT or MRI of the brain may be indicated to evaluate for toxic effects of methanol on the CNS
- Bilateral putaminal necrosis, with variable degree of bleeding, are a distinctive MRI finding
- Hypointensities in the putamen or caudate nucleus and optic pathway necrosis may be evident
Other diagnostic test findings
- Visual evoked response and electroretinography testing
- Diminished retinal sensitivity (a and b waveforms and cone response) along with scotomata may be observed in electroretinographic findings
- Visual evoked response may reveal normal P2 waveforms with evidence of decreased amplitude
General treatment items
- Initial management of poisoned patients should include maintenance of patent airway, sufficient ventilation, adequate circulation, correction of electrolyte imbalances, and improvement of hydration status
- Gastric decontamination using activated charcoal or gastric lavage is of little value as ingested methanol is rapidly absorbed from the GI tract
- Forced emesis using emetics like syrup of ipecac is contraindicated as there is an increased risk of aspiration of vomitus due to altered consciousness
- The primary goal is to assess whether methanol was ingested, the degree of the ingestion, and if present, administration of agents to inhibit its metabolism. In cases where significant metabolism has occurred with formic acid accumulation, hemodialysis will generally be indicated
- Ethanol, the most commonly used antidote, competes with methanol at the hepatic enzyme alcohol dehydrogenase, and inhibits the metabolism of methanol to formate
- Fomepizole, a potent inhibitor of the enzyme alcohol dehydrogenase, may be more effective and safer to administer. It is more expensive and has less clinical data supporting its use. However, favoring factors for use of this agent include the lack of CNS depression, lack of additional pancreatic toxicity, and simple dosing every 12 hours
- Fomepizole has a lower medication error rate than ethanol. Error-related harm was most commonly due to excessive ethanol dose or delayed antidote initiation
- Ethanol or fomepizole are indicated for treatment of methanol poisoning as per the following criteria suggested by the American Academy of Clinical Toxicology:
- Confirmed serum methanol concentration >20 mg/dL (>200 mg/L)
Or - Confirmed recent history of ingestion of toxic quantities of methanol and osmolal gap >10 mOsm/kg H2O
Or - History or strong clinical suspicion of methanol poisoning and at least two of the following criteria:
- Arterial pH < 7.3
- Serum bicarbonate < 20 meq/L (mmol/L)
- Osmolal gap > 10 mOsm/kg H2O
- Intermittent hemodialysis is recommended in cases of renal or nervous involvement so as to remove the methanol and organic acid anions (formate) from the blood as soon as possible
- Most treatment recommendations include use of sodium bicarbonate for correction of underlying metabolic acidosis when present. Theoretically, this decreases the amount of active formate and is felt to be beneficial in reversing visual deficits
Medications indicated with specific doses
Antidotes
- Ethanol [IV]
- Fomepizole [IV]
- Sodium bicarbonate [IV]
Dietary and Activity restrictions
- Limited activity is recommended in patients who are intoxicated, or who have altered level of consciousness, neurological movement deficits, hypotension, multi-organ failure, or visual impairment
Disposition
Admission Criteria
- Admission should occur if there is concern of methanol ingestion even in the absence of symptoms
- Intensive care unit (ICU) admission is generally indicated for all critically ill patients
- In the absence of hemodialysis or an antidote, patients must be urgently transferred to a different facility
Discharge Criteria
- Discharge can generally safely occur when symptoms subside, serum methanol level falls below 25 mg/dL, and acid/base and electrolyte status return to normal
Prevention
- Prevention strategies include safe handling, proper labeling of containers containing methanol, and use of child-resistant containers
- Persons handling methanol should use protective clothing and self-contained breathing apparatus to prevent accidental exposure
Prognosis
- Prognosis depends on the time to presentation and quantity of methanol ingested
- pH <7, bradycardia, coma at presentation, blood glucose >140 mg/dL (7.8 mmol/L), and >24 hours delay from intake to admission are predicators of poor prognosis
- Diagnostic and treatment delays may also contribute to poor outcome
Associated conditions
Pregnancy/Pediatric affects on condition
- Methanol poisoning in pregnant women has been rarely reported in literature
- Transplacental exposure to methanol may cause fatal methanol toxicity in the fetus
- Administration of ethanol for methanol poisoning treatment is contraindicated during the first trimester of pregnancy
- Fomepizole, a pregnancy category C drug, may be considered when the benefit outweighs the risk
Synonyms/Abbreviations
- Methanol toxicity
- Methanol intoxication
- Methanol ingestion
ICD-9-CM
- 980.1 Toxic effect of methyl alcohol
ICD-10
- T51.1 - Toxic effect of methanol
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